Human lymphoblastoid cells in culture will be used to determine uptake, influx and efflux of methotrexate under various conditions and the effect on it of 5-formyltetrahydrofolate (leucovorin) and 5-methyltetrahydrofolate. Transport of these reduced folates and the effect on it of methotrexate will also be studied. Metabolism of methotrexate to polyglutamate derivatives under various conditions and metabolism of the one-carbon and pteridine moieties of leucovorin and methyltetrahydrofolate under various conditions will be studied. The effect of methotrexate at various intracellular concentrations on various biosynthetic processes will be studied as well as the ability of various combinations of agents to rescue cells after exposure to methotrexate for various lengths of time and various external concentrations of methotrexate.